Treatment of herpesvirus associated primary effusion lymphoma with intracavity cidofovir.
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Publications and source records attributed to A Re.
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Oral cavity lymphoma (OCL) seems to occur more frequently in HIV-positive patients, but it is presently unknown whether HIV-related immune deficit plays a role in modifying the prevalence and the characteristics of these lymphomas. To clarify this issue, we compared OCL occurring in immunocompetent and HIV-positive patients. A comparison was made between cases of OCL occurring among 543 and 123 NHL consecutively diagnosed at a single center in immunocompetent and HIV-positive patients respectively. The prevalence of oral cavity involvement at diagnosis was significantly lower in the immunocompetent subgroup (HIV-negative: 1.66%; HIV-positive: 7.3%, P = 0.002). Extranodal T/NK nasal-nasal-type lymphoma (ET/NK-NL) was observed in 3 of 9 immunocompetent patients, whereas plasmablastic lymphoma (PBL) was observed in 3 of 9 HIV-positive patients. EBV expression correlated with HIV-positivity. Response to treatment was similar between the two subgroups, but the overall prognosis was significantly worse among HIV-positive patients. Median survival was 34 months in immunocompetent vs. 9 months in HIV-positive patients (P < 0.01). A higher frequency of oral cavity lymphoma was associated with HIV infection. ET/NK-NL and PBL seemed to be clinical entities characteristically related to immunocompetent and HIV-positive subgroups, respectively. Chemotherapy was feasible and effective in both subgroups, although a poor prognosis was associated with immunodeficiency.
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BACKGROUND: Unlike aggressive non-Hodgkin lymphoma (NHL), Hodgkin disease (HD) develops rarely in patients who are infected by human immunodeficiency virus (HIV), and its characteristics are not well defined. The authors analyzed the clinicopathologic and prognostic features from a consecutive series of patients with HIV-associated HD who were observed at their institution and compared them with the features observed in a concurrent series of patients with systemic HIV-related NHL. METHODS: Eighteen patients with HIV infection who were diagnosed and treated uniformly from 1985 to 1999 at a single primary referral center were analyzed. Their demographic, immunologic, and clinicopathologic features; responses to treatment; and outcomes were compared with those of 98 patients with systemic NHL of aggressive histology who were diagnosed during the same period and with 165 HIV negative patients with HD. RESULTS: HIV-associated HD and NHL occurred in patients with similar age, gender, HIV risk factors, degree of immunodeficiency, and incidence of previous acquired immunodeficiency syndrome. The clinical presentation of HIV-associated HD was atypical and was more aggressive than in HIV negative patients (mediastinal involvement, 11%; Stage III-IV, 84%; B symptoms, 83%). It was similar to HIV-related NHL, except for the frequency of extralymph node disease, which was seen less frequently in patients who had HD (56%) compared with patients who had NHL (82%; P = 0.025), and the frequency of bone marrow involvement, which was unexpectedly higher in patients who had HD (50%) compared with patients who had NHL (20%; P = 0.011). Potentially curative treatment was administered to 77% of patients with HD and 66% of patients with NHL. Complete remission and disease recurrence rates as well as disease free and overall survival rates did not differ significantly, with estimated overall survival at 5 years of 24% in patients with HD and 23% in patients with NHL. CONCLUSIONS: HIV-associated HD is an aggressive disease with demographic, clinical, and prognostic features nearly identical to those of HIV-related NHL.
OBJECTIVE: To determine if estrogen replacement therapy, in women with a history of endometrial cancer, increases the risk of recurrence or death from that disease. METHODS: Two hundred forty-nine women with surgical stage I, II, and III endometrial cancer were treated between 1984 and 1998; 130 received estrogen replacement after their primary cancer treatments and 49% received progesterone in addition to estrogen. Among this cohort, 75 matched treatment-control pairs were identified. The two groups were matched by using decade of age at diagnosis and stage of disease. Both groups were comparable in terms of parity, grade of tumor, depth of invasion, histology, surgical treatment, lymph node status, postoperative radiation, and concurrent diseases. The outcome events included the number of recurrences and deaths from disease. RESULTS: The hormone users were followed for a mean interval of 83 months (95% confidence interval [CI] 71.0, 91.4) and the nonhormone users were followed for a comparable mean interval of 69 months (CI 59.1, 78.7). There were two recurrences (1%) among the 75 estrogen users compared with 11 (14%) recurrences in the 75 nonhormone users. Hormone users had a statistically significant longer disease-free interval than nonestrogen users (P =.006). CONCLUSION: Estrogen replacement therapy with or without progestins does not appear to increase the rate of recurrence and death among endometrial cancer survivors.
Both the risk and the rate of development of atherosclerosis are increased in diabetics, but the mechanisms involved are unknown. Here we report a glucose-mediated increase in CD36 mRNA translation efficiency that results in increased expression of the macrophage scavenger receptor CD36. Expression of CD36 was increased in endarterectomy lesions from patients with a history of hyperglycemia. Macrophages that were differentiated from human peripheral blood monocytes in the presence of high glucose concentrations showed increased expression of cell-surface CD36 secondary to an increase in translational efficiency of CD36 mRNA. We obtained similar data from primary cells isolated from human vascular lesions, and we found that glucose sensitivity is a function of ribosomal reinitiation following translation of an upstream open reading frame (uORF). Increased translation of macrophage CD36 transcript under high glucose conditions provides a mechanism for accelerated atherosclerosis in diabetics.
BACKGROUND: The International Prognostic Index (IPI) effectively separates aggressive lymphomas into four groups with significantly different responses to therapy and survival. The authors have applied the IPI to evaluate a series of patients with human immunodeficiency virus (HIV) related lymphoma, a disease for which treatment strategies are still controversial and prognostic indicators are therefore particularly important. METHODS: Sixty-nine consecutive evaluable patients with HIV-related systemic non-Hodgkin lymphoma (NHL) diagnosed at a single Institution during a 10-year period were analyzed. Primary cerebral lymphoma was not considered. Forty-nine patients (71%) received aggressive combination chemotherapy (CT), 45 of whom were treated with the same program: cyclophosphamide, doxorubicin, etoposide, cytarabine, bleomycin, vincristine, and methotrexate with lecuovorin and prednisone (ProMACE-CytaBOM). Univariate and multivariate methods were used for statistical analysis. End points were response to treatment in patients receiving aggressive CT and survival of treated patients and all patients. RESULTS: According to age-adjusted IPI, 5 patients (7%) belonged to the low risk group, 12 (17%) to the low-intermediate risk group, 16 (23%) to the high-intermediate risk group, and 36 (52%) to the high risk group. Among the four groups with increasing IPI scores, the mean CD4 cell count at NHL diagnosis was 313, 230, 151, and 72/microL, respectively (P = 0.0085). The complete response (CR) rates were 100%, 88%, 50%, and 32% (P = 0. 0001) and the median survival of all patients was >60, 17, 10.9, and 6.8 months (P = 0.0002) for patients with low, low-intermediate, high-intermediate, and high risk IPI scores, respectively. In multivariate analysis, among patients receiving aggressive CT, high risk IPI (P = 0.013) and systemic symptoms (P = 0.014) were the only parameters related to CR, and high risk IPI (P = 0.016) and achievement of CR (P < 0.001) were the only parameters related to survival. When all patients were considered, high risk IPI had significant prognostic value for overall survival (P = 0.01), as did age (P = 0.019) and achievement of CR (P < 0.001). CONCLUSIONS: IPI was a reliable prognostic indicator in an unselected series of patients with HIV-related systemic NHL. The outcomes of patients without high risk IPI treated with aggressive CT were similar to those expected for HIV negative patients with lymphoma. However more than half of patients with HIV-related NHL had IPI high risk disease, and their outcomes were poor even after aggressive CT. The degree of immunodeficiency was related to increasing IPI score, suggesting that immunodeficiency may be an important factor contributing to the aggressive clinical presentation of lymphoma.
Acute disseminated encephalomyelitis (ADEM) is a demyelinating disorder of the central nervous system with an acute clinical onset and a wide variability in severity and outcome. It usually follows a viral infection or an immunization and is thought to be immuno- mediated. We report a case of ADEM with a dramatic clinical onset in an autologous peripheral blood stem cell transplant (PBSCT) recipient for non-Hodgkin's lymphoma who developed the neurologic syndrome 12 days after PBSC reinfusion. This is the first report of ADEM in the setting of autologous PBSCT, a therapeutic procedure performed with increasing frequency in a wide variety of hematologic and solid malignancies.
We describe the evaluation of the Bio-Rad BeTha Gene 1 kit (Bio-Rad Laboratories, Hercules, CA), a DNA-probe assay designed for the qualitative determination of the eight most common Mediterranean beta-thalassemia mutations. The kit utilizes the principle of allele-specific oligonucleotide (ASO) hybridization. Following sample preparation and in vitro DNA amplification by the polymerase chain reaction (PCR), an allele-specific detection of the amplified products by a nonradioactive enzymatic assay is performed. Genomic DNA is prepared from an individual's whole blood with a DNA purification matrix. In a second step, the beta-globin gene is amplified in a multiplex PCR reaction containing four 5' biotinylated oligonucleotide primers. In a final step, an aliquot of the PCR reaction is first chemically denatured and then captured in two eight-well strips of a 96-well enzyme-linked immunosorbent assay (ELISA) plate by hybridization to an immobilized ASO probe. Each DNA sequence at each of the eight mutation sites is represented by one normal and one mutant ASO. During this capture/hybridization step, which is performed at 37 degrees C, only perfectly matched PCR products will be captured by an ASO. Subsequently, the allele-specific captured biotin-labeled PCR products are detected by a colorimetric enzymatic reaction. The system permits the detection of 16 beta-thalassemia alleles using a high-throughput format that can be automated easily. A clinical feasibility study was performed to evaluate the functionality (method comparison study, assay validity using samples previously collected and stored at various temperatures for different periods of time, interference on kit performance, and assay validity for prenatal diagnosis) and the usability (ease of use, sample throughput) of the kit. The analysis of 110 samples previously studied with reference methods showed 100% clinical sensitivity and specificity. We demonstrate here that the procedure not only increases the throughput of beta-thalassemia allele genotyping but also provides an accurate, rapid, reliable, and nonisotopic diagnostic tool.
Successful autologous bone marrow transplantation (ABMT) and peripheral blood stem cell transplantation depend on safe hematopoietic stem cell (HSC) cryopreservation and storage. Several successful methods for cryopreservation and storage have been established and are commonly used all over the world. However, little is known about the effects of long-term cryopreservation on the capacity to sustain a complete immunohematopoietic engraftment. Several authors have investigated stem cell viability after cryopreservation and storage for more than 5 years and reported preclinical good viabilities in terms of dye-exclusion or colony-forming capability in vitro. Only two studies using BM cryopreserved for more than 5 years for transplantation are reported, but they did not provide proof of trilineage engraftment. In February 1997 at our institution, a patient with relapsed non-Hodgkin's lymphoma underwent ABMT with BM harvested in February 1990. He achieved a granulocyte count > 500 x 10(6)/L on day 21 and a self-supporting platelet count > 20 x 10(9)/L on day 30. After day 29, his hemoglobin level was satisfactory without need of transfusion support. This successful trilineage engraftment with cryopreserved BM that had been stored for 7 years suggests that HSC are able to maintain their capability to reconstitute hematopoiesis for a long time.
BACKGROUND AND OBJECTIVE: The use of hematopoietic growth factors in association with chemotherapy in human immunodeficiency virus (HIV)-related non-Hodgkin's lymphoma (NHL) has been recommended, but few studies have evaluated its cost-effectiveness. DESIGN AND METHODS: The effects of recombinant granulocyte colony-stimulating factor (G-CSF) were analyzed in 33 consecutive patients with HIV-related NHL treated at a single institution with the same chemotherapy program, ProMACE-CytaBOM, with G-CSF, in 21 cases diagnosed after December 31, 1991, or without G-CSF, in 12 cases diagnosed earlier. Pearson's chi-square analysis and the two-sided Student's t-test were used for statistical comparisons. The method of Kaplan-Meyer and the log-rank-test were used for survival analyses. RESULTS: G-CSF support significantly reduced the frequency of day-1 drug dose reductions (p < 0.001) and of chemotherapy delays (p < 0.001), and improved the actual delivered doses of adriamycin, cyclophosphamide and etoposide (p < 0.02). In patients with a CD4+ count < 0.01 x 10(9)/L, chemotherapy could be given at full doses in 90% of cycles with G-CSF compared to only 20% without it. G-CSF affected neither the frequency and duration of fever and hospitalization nor the complete remission and survival rates after stratification according to the CD4+ count. INTERPRETATION AND CONCLUSIONS: G-CSF support significantly improved dose-intensity in patients with HIV-related NHL treated with aggressive chemotherapy, particularly in the subgroup with a CD4+ count < 0.1 x 10(9)/L, but it did not improve their clinical outcome.
The purpose of this study was to estimate the relative risk of breast and colorectal cancers in women who were previously diagnosed with endometrial cancer. This study was conducted using a population-based cohort of 2347 women diagnosed with invasive cancer of the endometrium between January 1, 1984, and December 31, 1995 in Orange County, California. Only women with a diagnosis of invasive endometrial cancer at age 80 years old or below were included in the analysis (N = 2170). In this same cohort, metachronous and synchronous breast and colorectal cancers were ascertained and the risk of developing one or the other type of neoplasm was compared to the expected number of cases derived from cancer incidence in California by age, 1988-1992. We found a statistically increased risk of breast cancer as a second primary, while the observed incidence in colorectal risk did not reach statistical significance. The association between endometrial cancer and breast and possibly colorectal cancer indicates the importance of common etiologies for these cancers.
Umbilical cord blood (UCB) progenitor cells have been demonstrated to possess significant advantages over bone marrow (BM), in terms of proliferative capacity and immunologic reactivity. Therefore, UCB has been recently considered an attractive potential alternative to BM as a source of hematopoietic progenitor cells for clinical applications. Since several programs throughout the world are currently evaluating the feasibility of large-scale UCB banking for unrelated transplants, it was the aim of this study to evaluate whether cryopreservation procedures might heavily impair the clonogenic capacity, the feasibility of CD34+ selection and the ex vivo expansion potential of UCB progenitor cells. UCB samples were collected and cryopreserved as unseparated (n = 21) or mononuclear (MNC) cells (n = 15) within 12 h from delivery, and evaluated for viability, immunophenotype, cell and progenitor numbers after a minimum stay in liquid nitrogen of 6 months (range 6-14 months). Viability was always > 97% and no statistically significant difference was detected by flow cytometric analysis. Clonogenic recovery from unseparated cells was 80-87% for HPP-CFC, CFU-GEMM, BFU-E and CFU-GM, and from MNC cells ranged from 82 to 91% for LTC-IC, CFU-GEMM, BFU-E and CFU-GM. CD34+ selection (n = 8) was performed on fresh and cryopreserved MNC cells using the MiniMACS immunomagnetic separation device, showing no difference in yield (68 +/- 7% vs 57 +/- 4%, P < or = 0.4) or in purity (89 +/- 2% vs 81 +/- 6%, < or = 0.4), for fresh in comparison to cryopreserved MNC cells. After 14 days of liquid culture in the presence of different combinations of SCF, IL-3, IL-6 and G-CSF no statistically significant difference was detected in CFC fold-expansion for fresh or cryopreserved MNC cells and for CD34+ cells, either selected and cultured from fresh or cryopreserved MNC cells. In conclusion we can state that UCB is a potential source of primitive progenitor cells that can be cryopreserved unmanipulated or after physical separation without major losses in clonogenic capacity and immunophenotypic composition. Moreover, CD34+ selection from cryopreserved MNC cells is feasible and ex vivo expansion is not impaired. These results have important implications in the large scale UCB banking, in view of the potential applications of ex vivo expanded hematopoietic progenitor cells for the engraftment of adult patients.
The authors report a series of 7 patients undergoing surgical limb extension with a total of 9 segmentary extensions. The study focuses on the trend of 4 biohumoral parameters (ESR, PCR, leukocytes, neutrophil percentage) during the various stages of surgery. The authors conclude that, in conjunction with clinical assessment, these parameters represent a valid tool for monitoring infections during the course of extension. Of these parameters, PCR was found to be the most sensitive marker. If evaluated using the general trend of these markers, surgical limb lengthening is not dissimilar to the fracture healing process.
Squamous microcarcinomas of the uterine cervix represent a focus of controversy regarding a useful clinical definition. The confusion of terminology and numerous pathological definitions have led to a great variety of surgical treatments from the cone to the radical hysterectomy, with pelvic adenectomy. This report analyses retrospectively 133 cases of Stage IA cervical cancers which have been followed up for 10-240 months. The purpose of this work is to seek a uniform therapeutical approach to cervical microcarcinoma with the review of International Literature.
Recent reports suggest an increased incidence of endometrial cancer in breast cancer patients under long-term adjuvant tamoxifen (TAM) treatment. The Authors describe two cases of endometrial adenocarcinoma among 80 post-menopausal patients affected with breast cancer and treated with TAM.
Primary cancer of the vagina is one of the rarest malignant neoplasms: radiotherapy is the most frequently used treatment and local recurrences remain a constant problem. We describe a case of invasive squamous carcinoma of the vagina submitted to neoadjuvant therapy with carboplatinum. Pathological findings after surgery were completely negative for cancer.
In 20% of premenopausal breast cancer women on Tamoxifen (TAM) treatment there is an ovarian enlargement: in literature one case of acutely cystic ovaries is described. We observed 2 cases of acutely cystic ovaries in postmenopausal women surgically treated during a long-term adjuvant therapy with TAM.